An initial program of studies will investigate basic physiological actions of norepinephrine (NE) and serotonin (5-HT) in the somatosensory area of the cerebral cortex. The goal of these studies is to establish a basis for assessing noradrenergic and serotonergic function in two animal models of epilepsy; cortically kindled and genetically seizure-susceptible rats. Furthermore, tests used to examine biogenic amine function can be employed to clarify the mode of anticonvulsant drug action at synaptic levels within the cerebral cortex. A combination of microiontophoretic techniques, stimulation of biogenic amine and somatosensory afferent pathways and computer assisted analysis of peri-event histograms will be employed to quantitatively assess the effects of NE, 5-HT and several antiepileptic agents on cerebrocortical neuronal responsiveness to synaptic inputs and putative transmitter substances. The primary concept to be tested is that NE and 5-HT exert modulatory influences on synaptic efficacy within the cerebral cortx. Specific studies in animals with lowered convulsive thresholds will use the same protocols to assay for an alteration in cerebrocortical biogenic amine function which might correlate with increased seizure susceptibility. Anticonvulsant drug effects on synaptically mediated and transmitter induced cortical neuronal responses will be compared with NE/5-HT actions to determine if these compounds share in common mechanisms to modify transmission of information through cerebrocortical circuits. The proposed research will contribute to a basic understanding of noradrenergic and serotonergic function in the cerebral cortex and clarify the role of these biogenic amines in seizure disorders and mechanisms of anticonvulsant drug action